Genetic markers can help women with rheumatoid arthritis make informed decisions about pregnancy

When women with rheumatoid arthritis (RA) plan to become pregnant, many worry about whether they should stop their medications, risking a flare-up of their disease, or continue taking medications and risk possible damage to the baby.

About 50% to 75% will see their disease improve naturally during pregnancy for reasons yet unknown, while others may see a worsening of their RA. But they couldn’t have known what would happen to them.

Now, for the first time, Northwestern Medicine scientists have identified pre-pregnancy genetic markers that can predict who will get better and who will get worse.

The research was published this week in Research and therapy for arthritis.

RA is an incurable disease that affects 1% of the world’s adult population and is three times more common in women. It leads to significant disability due to inflammation of the joints and destruction of cartilage and bones.

“When women with RA become pregnant, there is often a natural improvement,” said lead researcher Damini Jawaheer, associate professor of medicine in rheumatology at Northwestern University Feinberg School of Medicine. “They describe it as ‘a miracle.’ They say, “I’ve never felt better with the medicine I’ve been taking.” But the cause of this improvement is a complete mystery.

“If women with RA can know in advance whether their disease is likely to resolve during pregnancy, they know they can stop taking their medications. Some RA medications are toxic and affect the fetus, while others are considered safe. But some women with RA don’t want to take RA medications during pregnancy, even those that are considered safe.”

Being able to predict who will get better and who will get worse will help women in their pregnancy planning and will also help ensure that treatment during pregnancy is targeted only to those women who are predicted to get worse, Jawaheer said . In addition, women who are predicted to improve, and their fetuses, will not be unnecessarily exposed to medications.

Jawaheer and her team found that before pregnancy, a group of white blood cells called neutrophils were highly expressed among the women who improved during pregnancy, and that some genes related to B cells were highly expressed among women who deteriorated.

This field hasn’t been well studied, in part because it’s difficult to find women for pregnancy screenings before they become pregnant, Jawaheer said.

She and colleagues were able to conduct the study because they had previously established a unique pregnancy cohort in Denmark, which enrolled women with RA and healthy women before pregnancy and followed them over time to determine who improved and who deteriorated. Using blood samples taken from these women before pregnancy, they examined the levels of several genes expressed in the blood. Blood samples were collected before pregnancy from 19 women with RA and 13 healthy women participating in the prospective pregnancy cohort.

Next, Jawaheer plans to conduct a study on a larger cohort of women to validate these findings. Additionally, her lab is trying to figure out why RA improves during pregnancy.

How does nature ensure that an incurable disease disappears? If we can understand how pregnancy produces natural improvement, we can use that as a model to develop a new drug that would be safer and could improve the lives of women and men living with this terrible disease.”

Damini Jawaheer, associate professor of medicine in rheumatology at Northwestern University Feinberg School of Medicine

The name of the paper is: “Pre-pregnancy gene expression traits are associated with subsequent improvement/worsening of rheumatoid arthritis during pregnancy.”

The other Northwestern author is Matthew Wright.

The study was funded by grants R21AR057931 and R01AR073111 from the National Institute of Arthritis, Musculoskeletal and Skin Diseases of the National Institutes of Health and by Gigtforeningen and Juliane Marie Center in Denmark.